Wnt signalling regulates paxillin ubiquitination essential for mesodermal cell motility

Area of Science:

• Developmental Biology
• Cell Biology
• Molecular Biology

Background:

• Gastrulation establishes vertebrate embryo architecture and germ layers.
• Convergent extension, driven by cell intercalation, shapes the mesoderm during Xenopus gastrulation.
• The non-canonical Wnt pathway regulates convergent extension, but specific molecular players remain unclear.

Purpose of the Study:

• To investigate the role of paxillin in Xenopus laevis gastrulation.
• To elucidate the regulatory mechanism of paxillin during mesodermal cell migration.
• To identify factors controlling paxillin stability in relation to Wnt signaling.

Main Methods:

• Xenopus laevis embryogenesis model system.
• Analysis of paxillin function and localization.
• Investigation of Wnt pathway regulation of paxillin ubiquitination and stability.
• Identification and characterization of the E3 ubiquitin ligase XRNF185.

Main Results:

• Paxillin is essential for mesodermal convergent extension movements in Xenopus.
• Wnt signaling controls paxillin ubiquitination and protein stability.
• The RING finger protein XRNF185 directly binds paxillin and the proteasome.
• XRNF185-mediated destabilization of paxillin promotes mesodermal cell migration.

Conclusions:

• Paxillin plays a critical role in Xenopus gastrulation by regulating mesodermal cell migration.
• A novel mechanism involving Wnt-controlled paxillin ubiquitination and stability is essential for convergent extension.
• XRNF185 acts as an E3 ubiquitin ligase targeting paxillin for degradation, facilitating embryonic morphogenesis.